共查询到20条相似文献,搜索用时 109 毫秒
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Ptprj is a candidate for the mouse colon-cancer susceptibility locus Scc1 and is frequently deleted in human cancers 总被引:21,自引:0,他引:21
Ruivenkamp CA van Wezel T Zanon C Stassen AP Vlcek C Csikós T Klous AM Tripodis N Perrakis A Boerrigter L Groot PC Lindeman J Mooi WJ Meijjer GA Scholten G Dauwerse H Paces V van Zandwijk N van Ommen GJ Demant P 《Nature genetics》2002,30(3):295-300
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Bop encodes a muscle-restricted protein containing MYND and SET domains and is essential for cardiac differentiation and morphogenesis 总被引:4,自引:0,他引:4
Gottlieb PD Pierce SA Sims RJ Yamagishi H Weihe EK Harriss JV Maika SD Kuziel WA King HL Olson EN Nakagawa O Srivastava D 《Nature genetics》2002,31(1):25-32
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Julien SG Dubé N Read M Penney J Paquet M Han Y Kennedy BP Muller WJ Tremblay ML 《Nature genetics》2007,39(3):338-346
We investigated the role of protein tyrosine phosphatase 1B (PTP1B) in mammary tumorigenesis using both genetic and pharmacological approaches. It has been previously shown that transgenic mice with a deletion mutation in the region of Erbb2 encoding its extracellular domain (referred to as NDL2 mice, for 'Neu deletion in extracellular domain 2') develop mammary tumors that progress to lung metastasis. However, deletion of PTP1B activity in the NDL2 transgenic mice either by breeding with Ptpn1-deficient mice or by treatment with a specific PTP1B inhibitor results in significant mammary tumor latency and resistance to lung metastasis. In contrast, specific overexpression of PTP1B in the mammary gland leads to spontaneous breast cancer development. The regulation of ErbB2-induced mammary tumorigenesis by PTB1B occurs through the attenuation of both the MAP kinase (MAPK) and Akt pathways. This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer. 相似文献
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Wildtype Kras2 can inhibit lung carcinogenesis in mice 总被引:13,自引:0,他引:13
Zhang Z Wang Y Vikis HG Johnson L Liu G Li J Anderson MW Sills RC Hong HL Devereux TR Jacks T Guan KL You M 《Nature genetics》2001,29(1):25-33
Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression. 相似文献
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p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway 总被引:4,自引:0,他引:4
Hui L Bakiri L Mairhorfer A Schweifer N Haslinger C Kenner L Komnenovic V Scheuch H Beug H Wagner EF 《Nature genetics》2007,39(6):741-749
The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional Mapk14 (also known as p38alpha) alleles, we investigated its function in postnatal development and tumorigenesis. When we specifically deleted Mapk14 in the mouse embryo, fetuses developed to term but died shortly after birth, probably owing to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha showed increased proliferation resulting from sustained activation of the c-Jun N-terminal kinase (JNK)-c-Jun pathway. Notably, in chemical-induced liver cancer development, mice with liver-specific deletion of Mapk14 showed enhanced hepatocyte proliferation and tumor development that correlated with upregulation of the JNK-c-Jun pathway. Furthermore, inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient hepatocytes and tumor cells. These results demonstrate a new mechanism whereby p38alpha negatively regulates cell proliferation by antagonizing the JNK-c-Jun pathway in multiple cell types and in liver cancer development. 相似文献
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Acetylation inactivates the transcriptional repressor BCL6 总被引:11,自引:0,他引:11
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Palstra RJ Tolhuis B Splinter E Nijmeijer R Grosveld F de Laat W 《Nature genetics》2003,35(2):190-194
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DNA methylation represses transcription in vivo. 总被引:9,自引:0,他引:9
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TGF-beta signaling in tumor suppression and cancer progression 总被引:44,自引:0,他引:44
Epithelial and hematopoietic cells have a high turnover and their progenitor cells divide continuously, making them prime targets for genetic and epigenetic changes that lead to cell transformation and tumorigenesis. The consequent changes in cell behavior and responsiveness result not only from genetic alterations such as activation of oncogenes or inactivation of tumor suppressor genes, but also from altered production of, or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor beta (TGF-beta) and its signaling effectors act as key determinants of carcinoma cell behavior. The autocrine and paracrine effects of TGF-beta on tumor cells and the tumor micro-environment exert both positive and negative influences on cancer development. Accordingly, the TGF-beta signaling pathway has been considered as both a tumor suppressor pathway and a promoter of tumor progression and invasion. Here we evaluate the role of TGF-beta in tumor development and attempt to reconcile the positive and negative effects of TGF-beta in carcinogenesis. 相似文献
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Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells 总被引:1,自引:0,他引:1
Stadtfeld M Apostolou E Ferrari F Choi J Walsh RM Chen T Ooi SS Kim SY Bestor TH Shioda T Park PJ Hochedlinger K 《Nature genetics》2012,44(4):398-405, S1-2